Mitochondrial translocation of EGFR regulates mitochondria dynamics and promotes metastasis in NSCLC

Ting Fang Che, Ching Wen Lin, Yi Ying Wu, Yu Ju Chen, Chia Li Han, Yih leong Chang, Chen Tu Wu, Tzu Hung Hsiao, Tse Ming Hong, Pan Chyr Yang

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Dysfunction of the mitochondria is well-known for being associated with cancer progression. In the present study, we analyzed the mitochondria proteomics of lung cancer cell lines with different invasion abilities and found that EGFR is highly expressed in the mitochondria of highly invasive non-small-cell lung cancer (NSCLC) cells. EGF induces the mitochondrial translocation of EGFR; further, it leads to mitochondrial fission and redistribution in the lamellipodia, upregulates cellular ATP production, and enhances motility in vitro and in vivo. Moreover, EGFR can regulate mitochondrial dynamics by interacting with Mfn1 and disturbing Mfn1 polymerization. Overexpression of Mfn1 reverses the phenotypes resulting from EGFR mitochondrial translocation. We show that the mitochondrial EGFR expressions are higher in paired samples of the metastatic lymph node as compared with primary lung tumor and are inversely correlated with the overall survival in NSCLC patients. Therefore, our results demonstrate that besides the canonical role of EGFR as a receptor tyrosine, the mitochondrial translocation of EGFR may enhance cancer invasion and metastasis through regulating mitochondria dynamics.

Original languageEnglish
Pages (from-to)37349-37366
Number of pages18
JournalOncotarget
Volume6
Issue number35
DOIs
Publication statusPublished - 2015

Fingerprint

Non-Small Cell Lung Carcinoma
Mitochondria
Mitochondrial Dynamics
Neoplasm Metastasis
Neoplasms
Pseudopodia
Epidermal Growth Factor
Polymerization
Proteomics
Lung Neoplasms
Up-Regulation
Adenosine Triphosphate
Lymph Nodes
Phenotype
Cell Line
Lung
Survival

Keywords

  • Cancer metastasis
  • EGFR
  • Mitochondria dynamics

ASJC Scopus subject areas

  • Oncology

Cite this

Che, T. F., Lin, C. W., Wu, Y. Y., Chen, Y. J., Han, C. L., Chang, Y. L., ... Yang, P. C. (2015). Mitochondrial translocation of EGFR regulates mitochondria dynamics and promotes metastasis in NSCLC. Oncotarget, 6(35), 37349-37366. https://doi.org/10.18632/oncotarget.5736

Mitochondrial translocation of EGFR regulates mitochondria dynamics and promotes metastasis in NSCLC. / Che, Ting Fang; Lin, Ching Wen; Wu, Yi Ying; Chen, Yu Ju; Han, Chia Li; Chang, Yih leong; Wu, Chen Tu; Hsiao, Tzu Hung; Hong, Tse Ming; Yang, Pan Chyr.

In: Oncotarget, Vol. 6, No. 35, 2015, p. 37349-37366.

Research output: Contribution to journalArticle

Che, TF, Lin, CW, Wu, YY, Chen, YJ, Han, CL, Chang, YL, Wu, CT, Hsiao, TH, Hong, TM & Yang, PC 2015, 'Mitochondrial translocation of EGFR regulates mitochondria dynamics and promotes metastasis in NSCLC', Oncotarget, vol. 6, no. 35, pp. 37349-37366. https://doi.org/10.18632/oncotarget.5736
Che, Ting Fang ; Lin, Ching Wen ; Wu, Yi Ying ; Chen, Yu Ju ; Han, Chia Li ; Chang, Yih leong ; Wu, Chen Tu ; Hsiao, Tzu Hung ; Hong, Tse Ming ; Yang, Pan Chyr. / Mitochondrial translocation of EGFR regulates mitochondria dynamics and promotes metastasis in NSCLC. In: Oncotarget. 2015 ; Vol. 6, No. 35. pp. 37349-37366.
@article{435120d6a62b47a09efcfb5783e546f8,
title = "Mitochondrial translocation of EGFR regulates mitochondria dynamics and promotes metastasis in NSCLC",
abstract = "Dysfunction of the mitochondria is well-known for being associated with cancer progression. In the present study, we analyzed the mitochondria proteomics of lung cancer cell lines with different invasion abilities and found that EGFR is highly expressed in the mitochondria of highly invasive non-small-cell lung cancer (NSCLC) cells. EGF induces the mitochondrial translocation of EGFR; further, it leads to mitochondrial fission and redistribution in the lamellipodia, upregulates cellular ATP production, and enhances motility in vitro and in vivo. Moreover, EGFR can regulate mitochondrial dynamics by interacting with Mfn1 and disturbing Mfn1 polymerization. Overexpression of Mfn1 reverses the phenotypes resulting from EGFR mitochondrial translocation. We show that the mitochondrial EGFR expressions are higher in paired samples of the metastatic lymph node as compared with primary lung tumor and are inversely correlated with the overall survival in NSCLC patients. Therefore, our results demonstrate that besides the canonical role of EGFR as a receptor tyrosine, the mitochondrial translocation of EGFR may enhance cancer invasion and metastasis through regulating mitochondria dynamics.",
keywords = "Cancer metastasis, EGFR, Mitochondria dynamics",
author = "Che, {Ting Fang} and Lin, {Ching Wen} and Wu, {Yi Ying} and Chen, {Yu Ju} and Han, {Chia Li} and Chang, {Yih leong} and Wu, {Chen Tu} and Hsiao, {Tzu Hung} and Hong, {Tse Ming} and Yang, {Pan Chyr}",
year = "2015",
doi = "10.18632/oncotarget.5736",
language = "English",
volume = "6",
pages = "37349--37366",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals LLC",
number = "35",

}

TY - JOUR

T1 - Mitochondrial translocation of EGFR regulates mitochondria dynamics and promotes metastasis in NSCLC

AU - Che, Ting Fang

AU - Lin, Ching Wen

AU - Wu, Yi Ying

AU - Chen, Yu Ju

AU - Han, Chia Li

AU - Chang, Yih leong

AU - Wu, Chen Tu

AU - Hsiao, Tzu Hung

AU - Hong, Tse Ming

AU - Yang, Pan Chyr

PY - 2015

Y1 - 2015

N2 - Dysfunction of the mitochondria is well-known for being associated with cancer progression. In the present study, we analyzed the mitochondria proteomics of lung cancer cell lines with different invasion abilities and found that EGFR is highly expressed in the mitochondria of highly invasive non-small-cell lung cancer (NSCLC) cells. EGF induces the mitochondrial translocation of EGFR; further, it leads to mitochondrial fission and redistribution in the lamellipodia, upregulates cellular ATP production, and enhances motility in vitro and in vivo. Moreover, EGFR can regulate mitochondrial dynamics by interacting with Mfn1 and disturbing Mfn1 polymerization. Overexpression of Mfn1 reverses the phenotypes resulting from EGFR mitochondrial translocation. We show that the mitochondrial EGFR expressions are higher in paired samples of the metastatic lymph node as compared with primary lung tumor and are inversely correlated with the overall survival in NSCLC patients. Therefore, our results demonstrate that besides the canonical role of EGFR as a receptor tyrosine, the mitochondrial translocation of EGFR may enhance cancer invasion and metastasis through regulating mitochondria dynamics.

AB - Dysfunction of the mitochondria is well-known for being associated with cancer progression. In the present study, we analyzed the mitochondria proteomics of lung cancer cell lines with different invasion abilities and found that EGFR is highly expressed in the mitochondria of highly invasive non-small-cell lung cancer (NSCLC) cells. EGF induces the mitochondrial translocation of EGFR; further, it leads to mitochondrial fission and redistribution in the lamellipodia, upregulates cellular ATP production, and enhances motility in vitro and in vivo. Moreover, EGFR can regulate mitochondrial dynamics by interacting with Mfn1 and disturbing Mfn1 polymerization. Overexpression of Mfn1 reverses the phenotypes resulting from EGFR mitochondrial translocation. We show that the mitochondrial EGFR expressions are higher in paired samples of the metastatic lymph node as compared with primary lung tumor and are inversely correlated with the overall survival in NSCLC patients. Therefore, our results demonstrate that besides the canonical role of EGFR as a receptor tyrosine, the mitochondrial translocation of EGFR may enhance cancer invasion and metastasis through regulating mitochondria dynamics.

KW - Cancer metastasis

KW - EGFR

KW - Mitochondria dynamics

UR - http://www.scopus.com/inward/record.url?scp=84947788132&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84947788132&partnerID=8YFLogxK

U2 - 10.18632/oncotarget.5736

DO - 10.18632/oncotarget.5736

M3 - Article

C2 - 26497368

AN - SCOPUS:84947788132

VL - 6

SP - 37349

EP - 37366

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 35

ER -